Pazopanib Zentiva: detailed information

Package leaflet: Information for the patient

Pazopanib Zentiva 200 mg film-coated tablets, 400 mg film-coated tablets

Equivalent medicine
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Pazopanib Zentiva is and what it is used for
What you need to know before taking Pazopanib Zentiva
How to take Pazopanib Zentiva
Possible side effects
How to store Pazopanib Zentiva
Contents of the pack and other information

1. What Pazopanib Zentiva is and what it is used for

Pazopanib Zentiva is a type of medicine called a protein kinase inhibitor. It works by blocking the action of proteins involved in the growth and spread of cancer cells.
Pazopanib Zentiva is used in adults to treat:

advanced renal cell carcinoma (a type of kidney cancer) or cancer that has spread to other organs.
certain types of soft tissue sarcoma, which is a type of tumour affecting the body's supportive tissues. It may occur in muscles, blood vessels, fatty tissue, or other tissues that support, surround, and protect the organs.

2. What you need to know before taking Pazopanib Zentiva

Do not take Pazopanib Zentiva

if you are allergic to pazopanib or to any of the other ingredients of this medicine (listed in section 6). Please check with your doctor if you think this applies to you.

Warnings and precautions
Talk to your doctor before taking Pazopanib Zentiva:

if you have a heart disease.
if you have a liver disease.
if you have previously had heart failure or a heart attack.
if you have previously had lung collapse.
if you have had problems related to bleeding, blood clots, or narrowing of the arteries.
if you have had stomach or intestinal problems, such as perforation (a hole) or fistula (an abnormal passage forming between parts of the intestine).
if you have thyroid problems.
if you have problems with kidney function.
if you have or have had an aneurysm (a bulging and weakening of a blood vessel wall) or a

tear in the wall of a blood vessel.
Tell your doctor if any of these apply to you. Your doctor will decide whether Pazopanib Zentiva is suitable for
you. You may need additional tests to check that your kidneys, heart, and liver are functioning properly.
High blood pressure and Pazopanib Zentiva
Pazopanib Zentiva can increase blood pressure. Your blood pressure will be monitored before starting and during treatment with Pazopanib Zentiva. If you have high blood pressure, you will be treated with medicines to lower it.

Tell your doctor if you have high blood pressure.

If you are about to undergo surgery
Your doctor will stop Pazopanib Zentiva at least 7 days before surgery, as the medicine may affect wound healing. Treatment will be restarted once the wound has healed adequately.
Conditions you should be aware of
Pazopanib Zentiva may worsen certain conditions or cause serious side effects. To reduce the risk of any problems, you should pay attention to certain symptoms while taking Pazopanib Zentiva. See section 4.
Children and adolescents
Pazopanib Zentiva is not recommended for people under 18 years of age. It is not yet known how it works in this age group. Furthermore, it must not be used in children under 2 years of age due to safety concerns.
Other medicines and Pazopanib Zentiva
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes herbal medicines and other medicines you can buy without a prescription.
Some medicines may affect how Pazopanib Zentiva works and may increase the likelihood of side effects. In turn, Pazopanib Zentiva may affect how other medicines work. These include:

clarithromycin, ketoconazole, itraconazole, rifampicin, telithromycin, voriconazole (used to treat infections).
atazanavir, indinavir, nelfinavir, ritonavir, saquinavir (used to treat HIV).
nefazodone (used to treat depression).
simvastatin and possibly other statins (used to treat high cholesterol levels).
medicines that reduce stomach acidity. The type of medicine you are taking to reduce stomach acidity (e.g. proton pump inhibitors, H-_2 antagonists, or antacids) may affect how you should take Pazopanib Zentiva. Talk to your doctor or nurse for advice.

Tell your doctor or pharmacist if you are taking any of these medicines.
Pazopanib Zentiva with food and drink
Do not take Pazopanib Zentiva with food, as this affects how the medicine is absorbed. Take it at least two hours after a meal or one hour before a meal (see section 3). Do not drink grapefruit juice while being treated with Pazopanib Zentiva, as this may increase the risk of side effects.
Pregnancy, breastfeeding and fertility
Pazopanib Zentiva is not recommended if you are pregnant. The effect of Pazopanib Zentiva during pregnancy is unknown.

Tell your doctor if you are pregnant or planning to become pregnant.
Use a reliable method of contraception while taking Pazopanib Zentiva, and for at least 2 weeks after stopping treatment, to prevent pregnancy.
If you become pregnant while being treated with Pazopanib Zentiva, inform your doctor.

You must not breastfeed while taking Pazopanib Zentiva. It is not known whether the components of Pazopanib Zentiva pass into breast milk. Discuss this with your doctor.
If you are a male patient (even if you have had a vasectomy) and have a partner who is pregnant or who could become pregnant (including those using other contraceptive methods), you must use a condom during sexual intercourse while taking Pazopanib Zentiva and for at least 2 weeks after the last dose.
Fertility may be affected by treatment with Pazopanib Zentiva. Talk to your doctor about this.
Driving and using machines
Pazopanib Zentiva may cause side effects that could affect your ability to drive or operate machinery.

Avoid driving or operating machinery if you feel confused, tired, weak, or if your energy levels are low.

Pazopanib Zentiva contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per film-coated tablet, i.e. essentially ‘sodium-free’.

3. How to take Pazopanib Zentiva

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
How much to take
Pazopanib Zentiva 200 mg film-coated tablets:
The recommended dose is four tablets of Pazopanib Zentiva 200 mg tablets (800 mg of pazopanib) taken once daily. This is the maximum daily dose. Your doctor may need to reduce the dose if you experience adverse effects.
Pazopanib Zentiva 400 mg film-coated tablets:
The recommended dose is two tablets of Pazopanib Zentiva 400 mg tablets (800 mg of pazopanib) taken once daily. This is the maximum daily dose. Your doctor may need to reduce the dose if you experience adverse effects.
When to take it
Do not take Pazopanib Zentiva with food. Take it at least two hours after a meal or one hour before a meal.
For example, you could take it two hours after breakfast or one hour before lunch. Take Pazopanib Zentiva every day at approximately the same time.
Swallow the tablets whole with water, one after the other. Do not break or crush the tablets, as this affects how the medicine is absorbed and may increase the risk of adverse effects.
If you take more Pazopanib Zentiva than you should
If you take too many tablets, contact your doctor or pharmacist for advice. If possible, show them the packaging or this leaflet.
If you forget to take Pazopanib Zentiva
Do not take a double dose to make up for a missed dose. Take only the next dose at the usual time.
Do not stop taking Pazopanib Zentiva without medical advice
Take Pazopanib Zentiva for as long as your doctor recommends. Do not stop unless your doctor tells you to.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Possible serious side effects
Brain swelling (reversible posterior leukoencephalopathy syndrome)
Pazopanib Zentiva may rarely cause brain swelling, which can be life-threatening. Symptoms include:

loss of speech
changes in vision
seizures (epileptic fits)
confusion
high blood pressure

Stop taking Pazopanib Zentiva and seek immediate medical help if you experience any of these symptoms, or if you have a headache accompanied by any of these symptoms.
Hypertensive crisis (sudden and severe increase in blood pressure)
Pazopanib Zentiva may occasionally cause a sudden and severe increase in blood pressure. This is known as a hypertensive crisis. Your doctor will monitor your blood pressure while you are taking Pazopanib Zentiva. Signs and symptoms of a hypertensive crisis may include:

severe chest pain
severe headache
blurred vision
confusion
nausea
vomiting
severe anxiety
shortness of breath
seizures (epileptic fits)
fainting
Stop taking Pazopanib Zentiva and seek immediate medical help if you develop a hypertensive crisis.

Heart problems
The risk of these problems may be higher in people with existing heart conditions or who are taking other medicines. You will be monitored for heart problems while taking Pazopanib Zentiva.
Heart dysfunction/heart failure, heart attack
Pazopanib Zentiva may affect the heart's pumping activity and may increase the likelihood of having a heart attack. Signs and symptoms include:

irregular or rapid heartbeat
fast heartbeat
fainting
chest pain or pressure
pain in arms, back, neck or jaw
shortness of breath
swelling in legs

Seek immediate medical help if you experience any of these symptoms.
Changes in heart rhythm (QT prolongation)
Pazopanib Zentiva may affect heart rhythm, which in some people may lead to a potentially serious heart condition known as torsade de pointes. This may result in a very rapid heartbeat causing sudden loss of consciousness.
Inform your doctor if you notice any unusual changes in your heartbeat, such as a heartbeat that is too fast or too slow.
Stroke
Pazopanib Zentiva may increase the likelihood of having a stroke. Signs and symptoms of stroke may include:

numbness or weakness on one side of the body
difficulty speaking
headache
dizziness
Seek immediate medical help if you experience any of these symptoms.

Bleeding
Pazopanib Zentiva may cause serious bleeding in the gastrointestinal tract (such as stomach, esophagus, rectum or intestine), or in the lungs, kidneys, mouth, vagina and brain, although this is not common. Symptoms include:

passing blood in stools or passing black stools
blood in urine
stomach pain
coughing or vomiting blood
Seek immediate medical help if you experience any of these symptoms.

Perforation and fistula
Pazopanib Zentiva may cause a tear (perforation) in the stomach or intestine, or the development of an abnormal connection between two parts of the digestive tract (a fistula). Signs and symptoms may include:

severe stomach pain
nausea and/or vomiting
fever
development of a hole (perforation) in the stomach or intestine, from which foul-smelling, bloody pus is released
Seek immediate medical help if you experience any of these symptoms.

Liver problems
Pazopanib Zentiva may cause liver problems that can lead to serious conditions such as liver dysfunction and liver failure, which may be fatal. Your doctor will monitor liver enzymes while you are taking Pazopanib Zentiva. Signs that the liver may not be working properly may include:

yellowing of the skin or whites of the eyes (jaundice)
dark urine
fatigue
nausea
vomiting
loss of appetite
pain in the right side of the stomach (abdomen)
easy bruising
Seek immediate medical help if you experience any of these symptoms.

Blood clots
Deep vein thrombosis (DVT) and pulmonary embolism
Pazopanib Zentiva may cause blood clots in the veins, especially in the legs (deep vein thrombosis or DVT), which may travel to the lungs (pulmonary embolism). Signs and symptoms may include:

sudden chest pain
shortness of breath
rapid breathing
leg pain
swelling of arms and hands or legs and feet

Thrombotic microangiopathy (TMA)
Pazopanib Zentiva may cause blood clots in small blood vessels in the kidneys and brain, accompanied by a decrease in red blood cells and cells involved in blood clotting (thrombotic microangiopathy, TMA). Signs and symptoms may include:

easy bruising
high blood pressure
fever
confusion
drowsiness
seizures (epileptic fits)
decreased urine output
Seek immediate medical help if you experience any of these symptoms.

Tumour lysis syndrome
Pazopanib Zentiva may cause rapid breakdown of tumour cells, leading to tumour lysis syndrome, which in some people may be fatal. Symptoms may include irregular heartbeat, seizures (fits), confusion, muscle cramps or spasms, or decreased urine production. Seek immediate medical help if you experience any of these symptoms.
Infections
Infections occurring while taking Pazopanib Zentiva may become severe. Symptoms of infections may include:

fever
flu-like symptoms such as cough, fatigue and body aches that do not go away
shortness of breath and/or wheezing
pain while urinating
cuts, scratches or wounds that are red, warm, swollen or painful
Seek immediate medical help if you experience any of these symptoms.

Lung inflammation
Rarely, Pazopanib Zentiva may cause inflammation of the lungs (interstitial lung disease, pneumonia), which in some people may be fatal. Symptoms include shortness of breath or cough that does not go away. While taking Pazopanib Zentiva, you will be monitored for lung problems.
Seek immediate medical help if you experience any of these symptoms.
Thyroid problems
Pazopanib Zentiva may reduce the amount of thyroid hormone produced by the body. This may cause weight gain and fatigue. While taking Pazopanib Zentiva, your thyroid hormone levels will be monitored.
Inform your doctor if you notice significant weight gain or fatigue.
Blurred or impaired vision
Pazopanib Zentiva may cause separation or tearing of the inner layer at the back of the eye (retinal detachment or tear). This may lead to blurred or impaired vision.
Inform your doctor if you notice any changes in vision.
Possible side effects (including possible serious side effects according to the relevant frequency category).
Very common side effects (may affect more than 1 in 10 people):

high blood pressure
diarrhoea
nausea or vomiting
stomach pain
loss of appetite
weight loss
taste disturbances or loss of taste
mouth pain
headache
tumour site pain
lack of energy, feeling weak or tired
change in hair colour
unusual hair loss or thinning
loss of skin pigment
skin rash, possibly with skin peeling
redness and swelling of the palms of the hands or soles of the feet
Inform your doctor or pharmacist if any of these side effects worsen or become bothersome.

Very common side effects that may be detected by blood or urine tests:

increased liver enzymes
reduced albumin in the blood
protein in the urine
reduced number of platelets in the blood (cells that help blood to clot)
reduced number of white blood cells in the blood

Common side effects (may affect up to 1 in 10 people)

indigestion, bloating, flatulence
nosebleeds
dry mouth or mouth ulcers
infections
abnormal drowsiness
difficulty sleeping
chest pain, shortness of breath, leg pain, and swelling of legs/feet. These may be signs of a blood clot in the body (thromboembolism). If the clot breaks loose, it may travel to the lungs and this may be life-threatening or even fatal.
the heart becomes less effective at pumping blood around the body (cardiac dysfunction)
slow heartbeat
bleeding from mouth, rectum or lung
dizziness
blurred vision
hot flushes
swelling of face, hands, ankles, feet or eyelids due to fluid retention
tingling, weakness or numbness in hands, arms, legs or feet
skin disorders, redness, itching, dry skin
nail disorders
burning, stinging, itching or tingling sensations on the skin
feeling cold, with chills
excessive sweating
dehydration
muscle, joint, tendon or chest pain, muscle spasms
hoarseness
shortness of breath
cough
coughing up blood
hiccups
collapsed lung with trapped air between the lung and chest wall, often causing shortness of breath (pneumothorax)
Inform your doctor or pharmacist if any of these side effects become bothersome.

Common side effects that may be detected by blood or urine tests:

reduced thyroid gland activity
liver function abnormalities
increased bilirubin (a substance produced by the liver)
increased lipase (an enzyme involved in digestion)
increased creatinine (a substance produced by muscles)
changes in blood levels of other various chemicals/enzymes. Your doctor will inform you of blood test results

Uncommon side effects (may affect up to 1 in 100 people)

stroke
temporary interruption of blood supply to the brain (transient ischaemic attack)
interruption of blood supply to part of the heart or heart attack (myocardial infarction)
interruption of blood supply to part of the heart (myocardial ischaemia)
blood clots accompanied by a decrease in red blood cells and cells involved in clotting (thrombotic microangiopathy, TMA). These may damage organs such as the brain and kidneys
increased number of red blood cells in the blood
sudden onset of shortness of breath, especially when accompanied by acute chest pain and/or rapid breathing (pulmonary embolism)
serious gastrointestinal bleeding (such as in stomach, oesophagus or intestine), or in kidneys, vagina and brain
heart rhythm disorders (QT prolongation)
hole (perforation) in the stomach or intestine
abnormal passage forming between parts of the intestine (fistula)
heavy or irregular menstrual periods
sudden sharp increase in blood pressure (hypertensive crisis)
inflammation of the pancreas (pancreatitis)
inflamed liver that is not functioning properly or is damaged
yellowing of the skin or whites of the eyes (jaundice)
inflammation of the lining of the abdominal cavity (peritonitis)
runny nose
skin rash that may be itchy or inflamed (flat or raised spots or blisters)
frequent bowel movements
increased sensitivity of the skin to sunlight
reduced sensitivity, especially of the skin
skin wound that does not heal (skin ulcer)

Rare side effects (may affect up to 1 in 1,000 people)

inflammation of the lungs ( pneumonia )
dilation and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and arterial dissections)

Not known (frequency cannot be estimated from the available data):

tumour lysis syndrome resulting from rapid breakdown of tumour cells
liver failure

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Pazopanib Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the bottle or blister pack and on the
carton after Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Pazopanib Zentiva contains
Pazopanib Zentiva 200 mg film-coated tablets:

The active substance is pazopanib (as hydrochloride). Each film-coated tablet contains 200 mg of pazopanib.
The other ingredients are: Tablet core: microcrystalline cellulose (E460), sodium starch glycolate (type A), povidone K30 (E1201), magnesium stearate (E470b). Tablet coating: hypromellose (E464), titanium dioxide (E171), macrogol 400 (E1521), iron oxide red (E172), polysorbate 80 (E433).

Pazopanib Zentiva 400 mg film-coated tablets:

The active substance is pazopanib (as hydrochloride).
Each film-coated tablet contains 400 mg of pazopanib.
The other ingredients are: Tablet core: microcrystalline cellulose (E460), sodium starch glycolate (type A), povidone K30 (E1201), magnesium stearate (E470b). Tablet coating: hypromellose (E464), titanium dioxide (E171), macrogol 400 (E1521), polysorbate 80 (E433).

Description of the appearance of Pazopanib Zentiva and pack sizes
Pazopanib Zentiva 200 mg film-coated tablets:
Pazopanib Zentiva 200 mg film-coated tablets are capsule-shaped, pink, with "200" printed on one side, approximately 14.3 mm x 5.7 mm in size.
Available in bottles of 30, 90, multiple pack of 90 (3 packs of 30 tablets).
Available in clear/transparent aluminium-PVC/PE/PVDC blisters of 30, 90, multiple pack of 90 (3 packs of 30 tablets).
Available in clear/transparent aluminium-PVC/PE/PVDC unit-dose divisible blisters of 30 x 1, 90 x 1, multiple pack of 90 x 1 (3 packs of 30 x 1 tablets).

Pazopanib Zentiva 400 mg film-coated tablets:
Pazopanib Zentiva 400 mg film-coated tablets are capsule-shaped, white, with "400" printed on one side, approximately 18.0 mm x 7.1 mm in size.
Available in bottles of 30, 60.
Available in clear/transparent aluminium-PVC/PE/PVDC blisters of 30, 60, multiple pack of 60 (2 packs of 30 tablets).
Available in clear/transparent aluminium-PVC/PE/PVDC unit-dose divisible blisters of 30 x 1, 60 x 1, multiple pack of 60 x 1 (2 packs of 30 x 1 tablets).
Not all pack sizes may be marketed.

Marketing Authorization Holder
Zentiva Italia S.r.l.
Via P. Paleocapa, 7
20121 Milano, Italy

Manufacturer
Remedica Ltd
Aharnon Street, Limassol Industrial Estate,
Limassol 3056, Cyprus
PharOS MT Ltd.
HF62X, Hal Far Industrial Estate,
Birzebbugia BBG3000, Malta

This medicinal product is authorized in the European Economic Area countries under the following names:
Hungary: Pazopanib Zentiva 200mg filmtabletta
Pazopanib Zentiva 400mg filmtabletta
Bulgaria: Пазопаниб Зентива 200mg филмирани таблетки
Пазопаниб Зентива 400mg филмирани таблетки
Estonia: Pazopanib Zentiva
Croatia: Pazopanib Zentiva 200 mg filmom obložene tablete
Pazopanib Zentiva 400 mg filmom obložene tablete
Lithuania: Pazopanib Zentiva 200 mg plėvele dengtos tabletės
Pazopanib Zentiva 400 mg plėvele dengtos tabletės
Latvia: Pazopanib Zentiva 200 mg apvalkotās tabletes
Pazopanib Zentiva 400 mg apvalkotās tabletes
Romania: PAZOPANIB ZENTIVA 200 mg comprimate filmate
PAZOPANIB ZENTIVA 400 mg comprimate filmate
Slovakia: Pazopanib Zentiva 200 mg
Pazopanib Zentiva 400 mg
Czech Republic: Pazopanib Zentiva
Denmark: Pazopanib Zentiva
Germany: Pazopanib Zentiva 200 mg filmtabletten
Pazopanib Zentiva 400 mg filmtabletten
Finland: Pazopanib Zentiva
France: Pazopanib Zentiva 200 mg comprimé pelliculé
Pazopanib Zentiva 400 mg comprimé pelliculé
Italy: Pazopanib Zentiva
Poland: Pazopanib Zentiva
Spain: Pazopanib Zentiva 200 mg comprimidos recubiertos con película EFG
Pazopanib Zentiva 400 mg comprimidos recubiertos con película EFG
Sweden: Pazopanib Zentiva
Norway: Pazopanib Zentiva